5 - Red cells and Anaemia Flashcards
Buffy coat
Leukocytes & platelets (<1% of total blood)
Red blood cells
- Made in bone marrow
- Small anuclear flexible biconcave disc shaped cells
- Most numerous cell in blood
- Generates energy through glycolytic pathway
How long do red blood cells last
120 days
Haem and globin
- Haem: Mitochondria, contains iron
- Globin: 4 polypeptide chains
Defects in globin
Thalassaemia and sickle cell disease
Blood cell production
Haemopoiesis
RBC production
Erythropoiesis
Erythropoiesis
Production of RBCs under influence of erythropoietin (EPO, produced in kidney)
Stages of RBC development in bone marrow
- Cell becomes smaller
- Nucleus matures (chromatin condensation)
- Cytoplasm gains haemoglobin
- Nucleus is extruded to produce mature RBC
- Newly formed RBC = reticulocyte
- RNA lost to become mature RBC
Erythropoietin (EPO)
- Hormone that regulates red blood cell production
- Produced in kidney
- Stimulated by renal O2 tension caused by anaemia, low atmospheric O2, defective cardiac or pulmonary function
Requirements for erythropoiesis
- Erythropoietin (EPO)
- Metals (iron, cobalt)
- Vitamins (B12, folate)
- Amino acids
- Other cytokines (IL3)
Iron
- Only 5-10% of iron intake is absorbed
- Binds in transferrin
- Require 1-2mg / day
- Excess stored in macrophages
Iron metabolism pathway
Duodenum and jejunum –> binds to transferrin –> bone marrow –> circulating haemoglobin –> Macrophages, liver, muscle myoepithelium
Vitamin B12 (Cobalamin)
- Required for nuclear maturation
- Dietary B12 combines with intrinsic factor (stomach)
- IF-B12 complex attaches to receptors in ileum
- Absorbed B12 binds to Transcobalamin II
- B12 carried to marrow and liver
Where does B12 come from
Meat, eggs, milk
Where does folate come from
Fruit and vegetables
Folate
- Required for nuclear maturation
- Absorbed in upper small intestine
- Small body stores (3-4 months)
- Deficiencies result in anaemia (macrocytic)
Red Blood Cell Membrane
- Deformable & stabile (navigate small vessels)
- Lipid bilayer with embedded proteins
- Proteins for membrane elasticity
- Proteins are embedded with lipids
How do RBCs die
- Removed in reticulo-endothelial system
- Iron released and stored as ferritin
- Globin chains are degraded to amino acids and returned to body pool
- Haem broken down to bilirubin and excreted by liver
Normal lifespan of RBcs
120 days
Haemolysis
Reduced RBc lifespan/increased rate of RBC destruction
Anaemia
A reduction in haemoglobin concentration below
normal range for age and gender of the individual
Is anaemia a disease
No but rather a manifestation of another disease
Clinical features of anaemia
- Paleness
- Lethargy
- Shortness of breath
- Tachycardia
- Fainting
- Low BP
Causes of anaemia
- Reduced bone marrow production of red cells
- Increased blood loss (haemorrhage)
- Increased RBC destruction (haemolysis)
Primary causes of anaemia
Bone marrow failure
Secondary causes of anaemia
Underlying problem reducing ability of the marrow to make red blood cells
Primary causes of reduced bone marrow production of red cells leading to anaemia
- Bone marrow failure (aplastic anaemia)
- Red cell aplasia
- Bone marrow dysfunction (myelodysplasia)
Secondary causes of reduced bone marrow production of red cells leading to anaemia
- Insufficient nutrients (iron, folate, B12, Erythropoietin)
- Infection
- Drugs
- Marrow infiltration (Leukaemia, cancer)
Iron deficiency causes
- Poor iron intake / dietary deficiency
- Poor iron absorption / malabsorption
- Chronic blood loss:
- Increased demand / iron utilisation
B12 deficiency causes
poor absorption (pernicious anaemia)
Folate deficiency
Poor diet, increased demands
Megaloblastic anaemia
- Caused by B-12 and folate deficiency
- Larger cells with delay in development of nucleus
Causes of haemorrhage leading to anaemia
- Acute (Accident, injury, surgery)
- Chronic (Malignancy, inherited platelet or bleeding disorder)
Causes of increased RBC destruction leading to anaemia
- Hereditary: Inherited defect of red cell membrane,
red cell enzymes or globin chains - Acquired: sepsis, microorganisms, liver or kidney disease, fragmentation haemolysis
Hereditary spherocytosis
- Common cause of inherited anaemia
- Defect of RBC membrane proteins
- RBCs more rigid than normal
- RBCs lack central pallor (spherocytes)
Defect of RBC membrane proteins that causes hereditary spherocytosis
Structural proteins spectrin, actin and band 3
Thalassaemia
Reduced production of a or b globin chains
Structural haemoglobinopathies
Abnormal globin chain structure (e.g. sickle cell anaemia)
Autoimmune haemolytic anaemia
An antibody directed against its own red blood cells. Caused by leukaemia and autoimmune diseases
Haemolytic anaemia due to infections
- Severe bacterial sepsis (causes RBCs to fragment)
- Malaria (Parasite inside red cell causes lysis)
- Clostridium welchii (Auto-antibody like haemolysis)
